The cephalosporin group of antibiotics has found widespread success in the treatment of bacterial infections. Cephalosporins generally have a much broader spectrum of activity than the penicillins, and have routinely been employed in situations where penicillin therapy is not indicated. More recently, a group of compounds that appears even more active antibacterially than the cephalosporins has been discovered. This new class of compounds is characterized as the 1-oxadethiacephalosporins.
While these compounds are in many respects superior to the cephalosporins, their widespread clinical use has been hindered by their high cost due to their difficulty of manufacture. For example, U.S. Pat. No. 4,220,766 describes a multi-step synthesis of certain 1-oxadethiacephalosporins starting from certain penicillin sulfoxides. Another multi-step synthesis is reported in U.S. Pat. No. 4,323,567.
Tsuji et al., in U.S. Pat. No. 4,220,766, found that a very useful intermediate in the synthesis of certain 1-oxadethiacephalosporins is an oxazoline derivative, namely an oxazoline bearing an allylic alcohol grouping. The reference teaches that such compounds can be cyclized in one step to a 1-oxadethiacephalosporin. However, the synthesis of the oxazoline involved numerous complicated steps. For example, the use of 3-exomethylene cephalosporin sulfoxides as starting materials in the synthesis of oxazolines is reported by Yanagisawa in Tetrahedron Letters, 23, pp. 3379-3382 (1982). That process involves the conversion of the cephalosporin sulfoxide to a heterocyclic disulfide derivative, which is subsequently converted to an oxazoline.
An object of this invention is to provide a one-step conversion of a 3-exomethylene cephalosporin sulfoxide to an oxazoline that bears an allylic alcohol substituent.